Association of Age and Sex With Multi-Modal Cerebral Physiology in Adult Moderate/Severe Traumatic Brain Injury: A Narrative Overview and Future Avenues for Personalized Approaches.

The impact of age and biological sex on outcome in moderate/severe traumatic brain injury (TBI) has been documented in large cohort studies, with advanced age and male sex linked to worse long-term outcomes. However, the association between age/biological sex and high-frequency continuous multi-modal monitoring (MMM) cerebral physiology is unclear, with only sparing reference made in guidelines and major literature in moderate/severe TBI. In this narrative review, we summarize some of the largest studies associating various high-frequency MMM parameters with age and biological sex in moderate/severe TBI. To start, we present this by highlighting the representative available literature on high-frequency data from Intracranial Pressure (ICP), Cerebral Perfusion Pressure (CPP), Extracellular Brain Tissue Oxygenation (PbtO2), Regional Cerebral Oxygen Saturations (rSO2), Cerebral Blood Flow (CBF), Cerebral Blood Flow Velocity (CBFV), Cerebrovascular Reactivity (CVR), Cerebral Compensatory Reserve, common Cerebral Microdialysis (CMD) Analytes and their correlation to age and sex in moderate/severe TBI cohorts. Then we present current knowledge gaps in the literature, discuss biological implications of age and sex on cerebrovascular monitoring in TBI and some future avenues for bedside research into the cerebrovascular physiome after TBI.

Tenderness and sympathy: distinct empathic emotions elicited by different forms of need.

Current need and vulnerability are two different forms of need. Integrating (a) cognitive-appraisal theories of emotion with (b) a view of human parental nurturance as emotionally based and cognitively generalizable, this article proposes that these two forms of need elicit distinct empathic emotions: Vulnerability evokes feelings of tenderness, whereas current need evokes feelings of sympathy. Results of two experiments support this proposal. Vulnerable targets elicited tenderness even when there was no current need; nonvulnerable targets did not. Sympathy was low when there was no evidence of current need but high when there was evidence of current need. Other forms of need and other empathic emotions are proposed, as are motivational and behavioral consequences of the distinction between tenderness and sympathy.

Neural responses to ingroup and outgroup members' suffering predict individual differences in costly helping.

Little is known about the neurobiological mechanisms underlying prosocial decisions and how they are modulated by social factors such as perceived group membership. The present study investigates the neural processes preceding the willingness to engage in costly helping toward ingroup and outgroup members. Soccer fans witnessed a fan of their favorite team (ingroup member) or of a rival team (outgroup member) experience pain. They were subsequently able to choose to help the other by enduring physical pain themselves to reduce the other's pain. Helping the ingroup member was best predicted by anterior insula activation when seeing him suffer and by associated self-reports of empathic concern. In contrast, not helping the outgroup member was best predicted by nucleus accumbens activation and the degree of negative evaluation of the other. We conclude that empathy-related insula activation can motivate costly helping, whereas an antagonistic signal in nucleus accumbens reduces the propensity to help.

An additional antecedent of empathic concern: valuing the welfare of the person in need.

Two experiments examined the role of valuing the welfare of a person in need as an antecedent of empathic concern. Specifically, these experiments explored the relation of such valuing to a well-known antecedent--perspective taking. In Experiment 1, both perspective taking and valuing were manipulated, and each independently increased empathic concern, which, in turn, increased helping behavior. In Experiment 2, only valuing was manipulated. Manipulated valuing increased measured perspective taking and, in part as a result, increased empathic concern, which, in turn, increased helping. Valuing appears to be an important, largely overlooked, situational antecedent of feeling empathy for a person in need.

The neural substrate of human empathy: effects of perspective-taking and cognitive appraisal.

Whether observation of distress in others leads to empathic concern and altruistic motivation, or to personal distress and egoistic motivation, seems to depend upon the capacity for self-other differentiation and cognitive appraisal. In this experiment, behavioral measures and event-related functional magnetic resonance imaging were used to investigate the effects of perspective-taking and cognitive appraisal while participants observed the facial expression of pain resulting from medical treatment. Video clips showing the faces of patients were presented either with the instruction to imagine the feelings of the patient ("imagine other") or to imagine oneself to be in the patient's situation ("imagine self"). Cognitive appraisal was manipulated by providing information that the medical treatment had or had not been successful. Behavioral measures demonstrated that perspective-taking and treatment effectiveness instructions affected participants' affective responses to the observed pain. Hemodynamic changes were detected in the insular cortices, anterior medial cingulate cortex (aMCC), amygdala, and in visual areas including the fusiform gyrus. Graded responses related to the perspective-taking instructions were observed in middle insula, aMCC, medial and lateral premotor areas, and selectively in left and right parietal cortices. Treatment effectiveness resulted in signal changes in the perigenual anterior cingulate cortex, in the ventromedial orbito-frontal cortex, in the right lateral middle frontal gyrus, and in the cerebellum. These findings support the view that humans' responses to the pain of others can be modulated by cognitive and motivational processes, which influence whether observing a conspecific in need of help will result in empathic concern, an important instigator for helping behavior.

Social neuroscience approaches to interpersonal sensitivity.

Interpersonal sensitivity refers to our ability to perceive and respond with care to the internal states (e.g., cognitive, affective, motivational) of another, understand the antecedents of those states, and predict the subsequent events that will result. This special issue brings together new research findings from empirical studies, including work with adults and children, genetics, functional neuroimaging, individual differences, and behavioral measures, which examine how we process and respond to information about our fellow individuals. By combining biological and psychological approaches, social neuroscience sheds new light on the complex and multi-faceted phenomenon of interpersonal sensitivity, including empathy. One should, however, be aware of the challenges and limits of such an approach.

"... As you would have them do unto you": Does imagining yourself in the other's place stimulate moral action?

Philosophers, psychologists, and religious teachers have suggested that imagining yourself in another's place will stimulate moral action. The authors tested this idea in two different situations. In Experiment 1, participants had the opportunity to assign themselves and another research participant to tasks, with one task clearly more desirable than the other. Imagining oneself in the other's place did little to increase the morality (fairness) of the decision. A different form of perspective taking, imagining the other's feelings, increased direct assignment of the other to the desirable task, apparently due to increased empathy. In Experiment 2, participants confronted a different decision: either accept an initial task assignment that would give them highly positive consequences and the other participant nothing or change the assignment so they and the other would each receive moderately positive consequences. In this situation, imagining oneself in the other's place did significantly increase moral action.

Moral hypocrisy: addressing some alternatives.

Two studies addressed alternative explanations for 3 pieces of evidence supporting the existence of moral hypocrisy. In Study 1, no support was found for the idea that low salience of social standards accounts for falsifying the result of a coin flip to assign oneself a more desirable task. In Study 2, no support was found for the idea that responses of those who honestly win the flip account for the higher ratings of morality of their action by participants who assign themselves the more desirable task after flipping the coin. Also, no support was found for the idea that responses of those who honestly win the flip account for the inability of personal moral responsibility measures to predict moral action. Instead, results of both studies provided additional evidence of moral hypocrisy.

C-terminal epitope tagging facilitates comparative ligand mapping from MHC class I positive cells.

Purification of specific class I molecules prior to peptide ligand characterization is complicated by the presence of multiple class I proteins in most cell lines. Immortalized B, T, and tumor cell lines typically express endogenous HLA-A, -B, and -C; and most individuals from which the cell lines are derived are heterozygous at these loci. Antibodies specific for a particular HLA molecule may be used for purification, but allele-specific antibodies can be biased by ligands occupying the peptide-binding groove. Through the use of C-terminal tagging, we have developed a method of soluble HLA production such that downstream purification does not skew the peptide analysis of the examined molecule. Comparison of peptides eluted from HLA class I molecules with and without C-terminal tags demonstrates that addition of a tag does not abrogate the peptide binding specificity of the original molecule. Both pooled Edman sequencing and mass spectrometric sequencing identified no substantial differences in peptides bound by untailed, 6-HIS-tailed, and FLAG-tailed class I molecules, demonstrating that the peptide specificity of a given molecule is not distorted by either tag. This production methodology bypasses problems with isolation of specific molecules and permits ligand mapping and epitope discovery in a variety of pathogen-infected and tumor cell lines.

Moral hypocrisy: appearing moral to oneself without being so.

How can people appear moral to themselves when they fail to act morally? Two self-deception strategies were considered: (a) misperceive one's behavior as moral and (b) avoid comparing one's behavior with moral standards. In Studies 1 and 2 the authors documented the importance of the 2nd strategy but not the 1st. Among participants who flipped a coin to assign themselves and another participant "fairly" to tasks, even a clearly labeled coin that prevented misperception did not produce a fair result (Study 1). Inducing behavior-standard comparison through self-awareness did (Study 2). Study 3 qualified the self-awareness effect: When moral standards were not salient before acting, self-awareness no longer increased alignment of behavior with standards. Instead, it increased alignment of standards with behavior and produced less moral action. Overall, results showed 3 different faces of moral hypocrisy.

Improving on-time performance in health care organizations: a case study.

In this paper, we propose a strategy to build a measurement system that helps improve on-time performance in health care organizations. We analyze the measurement system for monitoring the performance of daily start times of first surgeries in a U.S. hospital. Although surgeons appear to be the main cause of delay, efforts to improve their on-time performance alone are not sufficient to improve on-time performance for first surgeries. Therefore, working on the main source of delay to improve performance, as the Pareto principle suggests, does not always work in the health care context. Rather, we found that ameliorating the hospital's overall on-time performance achieves the desired result of improving surgeons' performance through a snowball effect (a self-reinforcing effect) and, consequently, the on-time performance for first surgeries also improves.

In a very different voice: unmasking moral hypocrisy.

Across 3 small studies, 80 female undergraduates were confronted with the dilemma of deciding whom-themselves or another research participant-to assign to a positive consequences task, leaving the other to do a dull, boring task. In Study 1, where morality was not mentioned, 16 of 20 assigned themselves to the positive consequences task, even though in retrospect only 1 said this was moral. In Studies 2 and 3, a moral strategy was suggested: either flipping a coin or accepting task assignment by the experimenter. In Study 2, 10 of 20 participants flipped a coin, but of these, 9 assigned themselves the positive consequences task. In Study 3, participants were significantly more likely to accept the experimenter's assignment when it gave them the positive consequences task. Overall, results suggested motivation to appear moral yet still benefit oneself. Such motivation is called moral hypocrisy.

Empathy and attitudes: can feeling for a member of a stigmatized group improve feelings toward the group?

Results of 3 experiments suggest that feeling empathy for a member of a stigmatized group can improve attitudes toward the group as a whole. In Experiments 1 and 2, inducing empathy for a young woman with AIDS (Experiment 1) or a homeless man (Experiment 2) led to more positive attitudes toward people with AIDS or toward the homeless, respectively. Experiment 3 tested possible limits of the empathy-attitude effect by inducing empathy toward a member of a highly stigmatized group, convicted murderers, and measuring attitudes toward this group immediately and then 1-2 weeks later. Results provided only weak evidence of improved attitudes toward murderers immediately but strong evidence of improved attitudes 1-2 weeks later.

Empathic joy and the empathy-altruism hypothesis.

Three experiments tested whether empathy evokes egoistic motivation to share vicariously in the victim's joy at improvement (the empathic-joy hypothesis) instead of altruistic motivation to increase the victim's welfare (the empathy-altruism hypothesis). In Experiment 1, Ss induced to feel either low or high empathy for a young woman in need were given a chance to help her. Some believed that if they helped they would receive feedback about her improvement; others did not. In Experiments 2 and 3, Ss induced to feel either low or high empathy were given a choice of getting update information about a needy person's condition. Before choosing, they were told the likelihood of the person's condition having improved--and of their experiencing empathic joy--was 20%, was 50%, or was 80%. Results of none of the experiments patterned as predicted by the empathic-joy hypothesis; instead, results of each were consistent with the empathy-altruism hypothesis.

Five studies testing two new egoistic alternatives to the empathy-altruism hypothesis.

The empathy-altruism hypothesis claims that prosocial motivation associated with feeling empathy for a person in need is directed toward the ultimate goal of benefiting that person, not toward some subtle form of self-benefit. We explored two new egoistic alternatives to this hypothesis. The empathy-specific reward hypothesis proposes that the prosocial motivation associated with empathy is directed toward the goal of obtaining social or self-rewards (i.e., praise, honor, and pride). The empathy-specific punishment hypothesis proposes that this motivation is directed toward the goal of avoiding social or self-punishments (i.e., censure, guilt, and shame). Study 1 provided an initial test of the empathy-specific reward hypothesis. Studies 2 through 4 used three procedures to test the empathy-specific punishment hypothesis. In Study 5, a Stroop procedure was used to assess the role of reward-relevant, punishment-relevant, and victim-relevant cognitions in mediating the empathy-helping relationship. Results of these five studies did not support either the empathy-specific reward or the empathy-specific punishment hypothesis. Instead, results of each supported the empathy-altruism hypothesis. Evidence that empathic emotion evokes altruistic motivation continues to mount.

Critical self-reflection and self-perceived altruism: when self-reward fails.

Social learning theory has produced a three-step model of prosocial development: In the young child, prosocial behavior is elicited by material rewards; in the older child, it is elicited also by social rewards; and in the morally mature adult, it is elicited by self-rewards based on an internalized perception of oneself as a kind, caring, altruistic individual. Self-perception theory has complicated this social learning model by demonstrating that once the third step is reached, the continued presence of material and social rewards may undermine intrinsic prosocial motivation based on self-rewards, producing moral regression. We propose a further complication. Critical self-reflection--the desire to know thyself, warts and all--may introduce a self-deprecating attributional bias that can undermine self-perceived altruism, even following helping for which one receives only intrinsic self-rewards. Two experiments are reported in which we manipulated critical self-reflection on one's reasons for helping. Results indicated that self-reflection undermined self-perceived altruism, especially when the salience of the self-rewards for helping was high. Experiment 2 also provided evidence that, as predicted, this self-reflection effect was most apparent for individuals who valued self-knowledge more highly than concern for others. Moral consequences of critical self-reflection are discussed.

Distress and empathy: two qualitatively distinct vicarious emotions with different motivational consequences.

The construct of empathy may be located conceptually at several different points in the network of interpersonal cognition and emotion. We discuss one specific form of emotional empathy--other-focused feelings evoked by perceiving another person in need. First, evidence is reviewed suggesting that there are at least two distinct types of congruent emotional responses to perceiving another in need: feelings of personal distress (e.g., alarmed, upset, worried, disturbed, distressed, troubled, etc.) and feelings of empathy (e.g., sympathetic, moved, compassionate, tender, warm, softhearted, etc.). Next, evidence is reviewed suggesting that these two emotional responses have different motivational consequences. Personal distress seems to evoke egoistic motivation to reduce one's own aversive arousal, as a traditional Hullian tension-reduction model would propose. Empathy does not. The motivation evoked by empathy may instead be altruistic, for the ultimate goal seems to be reduction of the other's need, not reduction of one's own aversive arousal. Overall, the recent empirical evidence appears to support the more differentiated view of emotion and motivation proposed long ago by McDougall, not the unitary view proposed by Hull and his followers.

Social evaluation and the empathy-altruism hypothesis.

Archer, Diaz-Loving, Gollwitzer, Davis, and Foushee (1981) suggested that feeling empathy for a person in need may lead to increased helping because the empathic individual wants to avoid negative social evaluation. As support for this suggestion, they claimed that empathy leads to increased helping only under socially evaluative circumstances. We conducted two studies to test this claim. In Study 1 subjects were led to believe that no one--including the person in need--would ever know if they declined to help. In this situation, which was designed to be totally devoid of the potential for negative social evaluation for not helping, there was still a positive relationship between self-reported empathic emotion and offering help. In Study 2 empathy (low versus high) and social evaluation (low versus high) were manipulated in a 2 X 2 design. Once again there was a positive relationship between empathy and offering help when the potential for social evaluation was low as well as high. Results of both studies, then, suggest that the motivation to help evoked by empathy is not egoistic motivation to avoid negative social evaluation. Instead, the observed pattern was what would be expected if empathy evokes altruistic motivation to reduce the victim's need.